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Alvarez, Y. D.

Publications and source records attributed to Alvarez, Y. D..

3 recordsLinked to original sources

Quantitative live imaging reveals PRICKLE1 controls junctional neural tube morphogenesis independent of Planar Cell Polarity

Neurulation, the process that forms the neural tube--the precursor to the brain and spinal cord--is frequently disrupted in congenital malformations. Primary and secondary neurulation are integrated at a junctional zone, yet the cellular dynamics linking these programs remain unknown. Using high-resolution quantitative live imaging in transgenic quail embryos, we show that the junctional neural tube forms through two coordinated processes: mediolateral convergence and EMT-driven ingression of medial neuroepithelial cells. We demonstrate that PRICKLE1, a core PCP protein, orchestrates these behaviors independently of planar polarity cues. PK1 is enriched at the apical cortex of medial cells, where it drives actomyosin accumulation and apical constriction. This function is essential for both convergence and cell ingression but is uncoupled from classical PCP axis establishment. Our findings redefine the molecular basis of junctional neurulation and implicate impaired EMT as a central cause of localized neural tube defects.

developmental biology↗

Genomic mosaicism reveals developmental organization of trunk neural crest-derived ganglia

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia. Highlights- Genetic mosaicism and real-time imaging reveal trunk neural crest cellular dynamics. - DRG or SG cells from different axial levels are more lineage-related than from the same level. - Cell fate specification of trunk neural crest progenitors occurs before neural tube delamination. - These aspects of clonal organization are evolutionarily conserved across mammals and avians.

developmental biology↗

The Lifeact-EGFP Quail: A New Avian Model for Studying Actin Dynamics In Vivo

Here we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis. Using high-resolution live imaging approaches, we present the dynamic behaviours and morphologies of cellular protrusions in different tissue contexts. Furthermore, through the integration of live imaging with computational segmentation, we reveal the dynamics of cells undergoing apical constriction and the emergence of large-scale actin structures such as supracellular cables and rosettes within the neuroepithelium. These findings not only enhance our understanding of tissue morphogenesis but also demonstrate the utility of the Lifeact-EGFP transgenic quail as a new model system for live in vivo investigations of the actin cytoskeleton.

developmental biology↗